Oral cancer incidence and mortality rates for African-Americans are notably higher than those of U.S. whites. Genetic differences by race may explain a portion of the observed excess risk. The primary aim of this Phase Il project is to test whether the expression of three candidate oncogenes (p53, ras, HER-2/neu) in frankly malignant oral epithelium differs by race [black / white] with and without controlling for differences in other potential covariates. Secondary aims will focus on (a) detecting differences by race in the expression of the candidate oncogenes in dysplastic tissue from individuals diagnosed with oral epithelial dysplasia (OED)(but without a history of oral cancer), (b) measuring the association between the expression of the three candidate oncogenes and known or suspected risk factors for oral cancer and OED among individuals diagnosed with those lesions, (c) estimating the relative risk by race of oral cancer and both smoking and drinking among individuals whose tumors are (i) oncogene-positive or (ii) oncogene- negative, (d) detecting differences by race in (i) depression and (ii) attitudes and values regarding oral and general health among individuals diagnosed with oral cancer, OED, or a benign oral tumor (i.e., an irritation fibroma). Based upon promising relationships between race and oncogene expressivity observed during the initial years of the Phase Il study, specific mutational patterns in the respective candidate oncogenes will be characterized by molecular-genetic techniques. To address the above aims, this project will expand upon an Epidemiologic Database / Biopsy Specimen Repository (EDBSR) initiated during Phase I developmental grant. The EDBSR will store (a) formalin-fixed, paraffin- embedded biopsy specimen slides available from subjects who have been histopathologically diagnosed with oral cancer or oral epithelial dysplasia through a participating pathology laboratory and (b) risk factor exposure / behavioral information obtained using standardized questionnaires from the same oral cancer and OED cases as well as from individuals diagnosed with an irritation fibroma (i.e., the control series). The availability of such data allows for the concomitant analysis of epidemiologic and biomarker information with sample sizes large enough to provide for satisfactory power when evaluating genetic and environmental determinants of oral cancer and OED by race. An additional advantage of the EDBSR is that it will serve as an invaluable "testing ground" as new oncogenes and biomarkers are identified in the future.